Howard Fearnhead 

Dr Howard Fearnhead

 

Career History

 

1999-2004: Principal Investigator, National Cancer Institute, NIH, Maryland, USA
2004-2006: Senior researcher, National Centre of Biomedical Engineering Science, NUI Galway
2006-2008: Lecturer (below the bar) in Pharmacology and Therapeutics, NUI Galway
                            2008-present: Lecturer (above the bar) in Pharmacology and Therapeutics, NUI Galway

 

Research Interests

 

Caspase regulation


Cell death and differentiation


Drug-resistance in cancer cells

 

Research Overview

 

Around twenty years of research have defined the the molecular events of apoptosis that lead to cell death. Put simply, different molecular pathways, activated by diverse signals, converge on the activation of caspases. These proteases rapidly and irreversibly dismantle the condemned cell through the cleavage of specific substrates. From these studies emerged the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis. At the same time counter-intuitive data have emerged that suggest the model explaining the role of apoptosis in tumourigenesis and cancer therapy is far too simple. We are particularly interested in investigating the provocative idea that death-inducing caspases are far more versatile than previously thought, an idea that has important implications for how we view the role of apoptosis in a range of different processes including cell differentiation, tissue repair, tumourigenesis and cancer therapy.

 

Selection of key publications:

 

Jäger R, Fearnhead HO. "Dead Cells Talking": The Silent Form of Cell Death Is Not so Quiet. Biochem Res Int. 2012;2012:453838. doi: 10.1155/2012/453838. Epub 2012 Aug 7.

Martin AG, Trama J, Crighton D, Ryan KM, Fearnhead HO. Activation of p73 and induction of Noxa by DNA damage requires NF-kappa B. Aging (Albany NY). 2009 Feb 18;1(3):335-49.

O'Prey J, Crighton D, Martin AG, Vousden KH, Fearnhead HO, Ryan KM. p53-mediated induction of Noxa and p53AIP1 requires NFkappaB. Cell Cycle. 2010 Mar 1;9(5):947-52. Epub 2010 Mar 7.

Fabian Z, O'Brien P, Pajecka K, Fearnhead HO. TPCK-induced apoptosis and labelling of the largest subunit of RNA polymerase II in Jurkat cells. Apoptosis. 2009 Oct;14(10):1154-64. doi: 10.1007/s10495-009-0386-y.

Malladi S, Challa-Malladi M, Fearnhead HO, Bratton SB. The Apaf-1*procaspase-9 apoptosome complex functions as a proteolytic-based molecular timer. EMBO J. 2009 Jul 8;28(13):1916-25. doi: 10.1038/emboj.2009.152. Epub 2009 Jun 4.

Murray TV, McMahon JM, Howley BA, Stanley A, Ritter T, Mohr A, Zwacka R, Fearnhead HO. A non-apoptotic role for caspase-9 in muscle differentiation. J Cell Sci. 2008 Nov 15;121(Pt 22):3786-93. doi: 10.1242/jcs.024547. Epub 2008 Oct 28.

Samali A, O'Mahoney M, Reeve J, Logue S, Szegezdi E, McMahon J, Fearnhead HO. Identification of an inhibitor of caspase activation from heart extracts; ATP blocks apoptosome formation. Apoptosis. 2007 Mar;12(3):465-74.

Chandra D, Bratton SB, Person MD, Tian Y, Martin AG, Ayres M, Fearnhead HO, Gandhi V, Tang DG. Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome C and inhibiting apoptosome. Cell. 2006 Jun 30;125(7):1333-46.

Martin AG, Fearnhead HO. Apocytochrome c blocks caspase-9 activation and Bax-induced apoptosis. J Biol Chem. 2002 Dec 27;277(52):50834-41. Epub 2002 Oct 18.

Fearnhead HO, Rodriguez J, Govek EE, Guo W, Kobayashi R, Hannon G, Lazebnik YA. Oncogene-dependent apoptosis is mediated by caspase-9. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13664-9.

Fearnhead HO, McCurrach ME, O'Neill J, Zhang K, Lowe SW, Lazebnik YA. Oncogene-dependent apoptosis in extracts from drug-resistant cells. Genes Dev. 1997 May 15;11(10):1266-76.

 

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